FLAGYL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FLAGYL (FLAGYL).
Metronidazole, a nitroimidazole antibiotic, enters bacterial cells and is reduced to cytotoxic intermediates that damage DNA and inhibit nucleic acid synthesis, leading to cell death. It is active against anaerobic bacteria and protozoa.
| Metabolism | Hepatic metabolism via oxidation and glucuronidation; major metabolites include hydroxy metabolite (active) and acid metabolite. CYP450 enzymes involved (CYP2A6, CYP2C9, CYP3A4). |
| Excretion | Renal: 60-80% of dose excreted unchanged in urine; biliary/fecal: 6-15% as metabolites and unchanged drug; enterohepatic circulation contributes to prolonged elimination. |
| Half-life | Terminal elimination half-life: 6-8 hours in adults with normal renal function; prolonged to 7-21 hours in hepatic impairment; no significant change in renal impairment; clinically relevant for dosing interval (usually 8-hourly). |
| Protein binding | Less than 20% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | Volume of distribution: 0.6-0.8 L/kg (approximately 40-60 L in adults), indicating extensive tissue penetration; exceeds total body water, consistent with distribution into all tissues including abscess cavities and CNS. |
| Bioavailability | Oral bioavailability: 80-100% (well absorbed); IV bioavailability: 100% (by definition); Topical: Systemic absorption minimal (<2%). |
| Onset of Action | Oral: Onset of clinical effect within 1-2 hours after dose; IV: Immediate after infusion, with therapeutic concentrations achieved within 30 minutes; Topical: Clinical response may take 2-5 days. |
| Duration of Action | Duration: Approximately 12-24 hours after a single dose, depending on dose and route; clinical effects persist for 8-12 hours for infections due to sustained tissue levels. |
| Action Class | 5-Nitroimidazole (Antiprotozoal & Antibacterial) |
| Brand Substitutes | Metrogyl Suspension |
Metronidazole 500 mg intravenously every 8 hours or 500 mg orally every 8 hours.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (GFR >10 mL/min). For severe renal impairment (GFR <10 mL/min), reduce dose to 500 mg every 12 hours. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50% (e.g., 250 mg every 8 hours). Child-Pugh C: reduce dose to 250 mg every 12 hours. |
| Pediatric use | 15-50 mg/kg/day intravenously or orally divided every 8 hours, depending on infection type and severity. Maximum 4 g/day. |
| Geriatric use | Monitor renal function; same dosing as adults unless severe renal impairment (CrCl <10 mL/min) requires dose reduction to 500 mg every 12 hours. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for FLAGYL (FLAGYL).
| Breastfeeding | Metronidazole is excreted into breast milk with an M/P ratio of approximately 0.9-1.5. After a single 2 g oral dose, peak milk concentration ~10-20 mcg/mL. The American Academy of Pediatrics considers it compatible with breastfeeding, but because of potential mutagenicity, avoid high doses (e.g., 2 g single dose) for 12-24 hours; resume breastfeeding after 2-3 half-lives. Lower doses (250-500 mg) are considered safe. |
| Teratogenic Risk | Flagyl (metronidazole) crosses the placenta. In the first trimester, use is generally avoided due to theoretical risk of teratogenicity, but data from large cohort studies do not show a significant increase in major malformations (risk category B). In the second and third trimesters, no fetal harm has been demonstrated; however, use only if clearly needed. High doses associated with fetal toxicity in animals. |
■ FDA Black Box Warning
Carcinogenicity: Metronidazole has been shown to be carcinogenic in mice and rats. Chromosomal aberrations have been reported in patients with Crohn's disease and other conditions. Use should be reserved for approved indications only.
| Serious Effects |
["Hypersensitivity to metronidazole or other nitroimidazole derivatives","First trimester of pregnancy (avoid; use during later trimesters only if clearly needed)","Breastfeeding (discontinue drug or bottle-feed; excreted in breast milk)","History of blood dyscrasias","Concurrent use of disulfiram (psychotic reactions may occur; wait at least 2 weeks after disulfiram)","Concurrent use of propylene glycol-containing IV formulations in neonates or patients with renal impairment"]
| Precautions | ["Carcinogenicity risk (see black box warning)","Neurologic effects: peripheral neuropathy, seizures, encephalopathy; discontinue if abnormal neurologic signs occur","Hematologic effects: leukopenia, neutropenia; monitor CBC","Hepatic impairment: dosage adjustment recommended","Metronidazole may cause metallic taste, dark urine, and disulfiram-like reaction with alcohol","Prolonged use may result in superinfection (e.g., C. difficile diarrhea)","Potential for ethylene glycol toxicity if administered with propylene glycol-containing solutions"] |
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| Fetal Monitoring | Monitor maternal liver function (AST, ALT) due to rare hepatotoxicity; complete blood count if therapy exceeds 10 days. Fetal monitoring with ultrasound if used in pregnancy for prolonged courses. No specific fetal monitoring required for short-term use. |
| Fertility Effects | No known adverse effects on fertility in humans. In animal studies, no impairment of fertility at therapeutic doses. |